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D-serine: physiology and pathology
Inna Radzishevsky1, Hagit Sason, Herman Wolosker
1Department of Biochemistry, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Purpose Of Review:
Here, we discuss the recent data on the role of different N-methyl D-aspartate receptor (NMDAR) coagonists, D-serine and glycine, in regulating NMDAR activity and neurotoxicity.
Recent Findings:
D-Serine originates from both neurons and astrocytes, from where it is released by different mechanisms. Recent data indicate that like glial D-serine, neuronal D-serine is required for NMDAR-dependent, long-term potentiation at the hippocampal CA1-CA3 synapses and proper synapse formation in the cerebral cortex. D-serine is the physiological coagonist of synaptic NMDAR, whereas glycine action is restricted to extrasynaptic sites.
Summary:
D-Serine is now recognized as the major NMDAR coagonist at the synapse. The data establish D-serine as a key transmitter or neuromodulator that mediates synaptic NMDAR activation and neurotoxicity. In this context, drugs that inhibit D-serine synthesis or release will provide new neuroprotective strategy.
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